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\begin{document}

\title{Clostridium sordellii: A cause of toxic shock syndrome after a breach in
the GI tract}



\author[1]{Sydney Pence}%
\author[2]{Rajshri Joshi}%
\author[2]{Kasturi Shrestha}%
\affil[1]{Ohio University}%
\affil[2]{Cleveland Clinic Akron General}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\emph{Clostridium sordellii}\textbf{: A cause of toxic shock syndrome
after a breach in the GI tract}

Sydney Pence,\textsuperscript{1} Rajshri
Joshi,\textsuperscript{2}Kasturi Shrestha\textsuperscript{3}

1. Ohio University Heritage College of Osteopathic Medicine, 4180
Warrensville Center Rd, Warrensville Heights, OH 44122. Email:
sp883713@ohio.edu

2. Internal Medicine, Cleveland Clinic Akron General, 1 Akron General
Ave, Akron, OH 44307. Email: JOSHIR4@ccf.org

3. Infectious Disease, Cleveland Clinic Akron General, 1 Akron General
Ave, Akron, OH 44307. Email: SHRESTK2@ccf.org

\emph{Corresponding Author Information:}

Rajshri Joshi: 1 Akron General Ave, Ambulatory Care Center, Bldg. 301,
Fl5, Akron Ohio 44307

Tel: 330-344-6015

Fax: 330-344-6820

Email: \emph{joshir4@ccf.org}

There were no sources of financial support for this case report. Patient
consent was obtained. We have no conflicts of interest to report, or
acknowledgements to declare.

\emph{ABSTRACT}

When found in humans, \emph{Clostridium sordellii} is most often
associated with infections of the uterus and perineum. This organism is
highly virulent, causing tissue necrosis, leukemoid reactions, and
death. This report describes an interesting case of \emph{Clostridium
sordellii} causing toxic shock syndrome post translocation through the
GI tract.

\emph{KEYWORDS:} \emph{Clostridium sordelli} ; infectious disease
medicine; shock, septic; leukemoid reaction

\emph{}

\emph{INTRODUCTION}

\emph{Clostridium sordellii,} first identified in 1922 by Alfredo
Sordelli, is a beta hemolytic anaerobic gram-positive spore forming
rod\textsuperscript{1,2}. It is typically found in soil and the gut of
many animals, including humans \textsuperscript{1}. When found
pathologically in humans, \emph{C. sordellii} is almost exclusively
reported with infections of the uterus and perineum; however, there have
been rare cases of infection in other locations of the body reported
post-operatively \textsuperscript{1,3} or with intravenous drug
use\textsuperscript{4,5}. In most of the cases of
\emph{Clostridial}bacteremia, patients were predisposed to infection
because of their compromised immune system or underlying malignancy
\textsuperscript{6}. Suppressed immune system in many has also been a
cause of delayed presentation of signs of infection thus making the
organism invariably fatal.

Unfortunately, \emph{C. sordelli} is highly virulent, causing death in
nearly 70\% of cases \textsuperscript{1,7}. Its virulence is achieved
with exotoxins, primarily the lethal and hemorrhagic
toxins\textsuperscript{1}. Infection with \emph{C. sordelli} typically
causes an acute onset leukemoid reaction accompanied by hypotension and
tachycardia. Some reports have demonstrated this pathogen to cause a
capillary leak syndrome, leading to
hemoconcentration\textsuperscript{1}. Even more severely, there have
been reports of\emph{C. sordelli} , almost exclusively involving the
uterus or perineum, causing toxic shock syndrome \textsuperscript{3,8}.

Little guidance exists regarding the treatment of \emph{C.
sordelli;}although, some studies suggest that the infection is
responsive to beta-lactams, clindamycin, tetracycline, and
chloramphenicol\textsuperscript{9}.

This report presents a recent case that highlights the diagnosis and
treatment of \emph{Clostridium sordellii} causing toxic shock syndrome
in the setting of a hemorrhagic necrotic renal mass and its
fistulization with the adjacent splenic flexure of the colon. This is
the first report of its kind.

\emph{CASE REPORT}

A 69-year-old man presented to the emergency room with back pain and
uncontrollable shaking. His past medical history was significant for
metastatic renal cell carcinoma, a penicillin allergy, and surgical
history of small bowel obstruction two weeks after undergoing transverse
colostomy and one week post-renal biopsy. On physical exam, the patient
was confused and found tachycardic, tachypneic, hypotensive, and
febrile. Pertinent labs included lactate of 8mmol/L (0.5-2.2 mmol/L),
initial hemoglobin of 10g/dL that fell to 7.7g/dl (11.5 - 15.5 g/dL),
and a WBC count of 16,000/mL (4,500-11,000/mL). CT scan showed a left
necrotic, hemorrhagic renal mass invading the adjacent splenic flexure
of the colon. Invasion of the pancreatic tail and left adrenal gland
with distal splenic vessels coursing through the mass could also not be
excluded (Figure 1). The patient received one dose of aztreonam,
vancomycin, metronidazole, and levofloxacin in the emergency department.
Piperacillin/Tazobactam was not used given the patient's history of
penicillin allergy.

After the patient was admitted to the intensive care unit for septic
shock, he was treated with an antibiotic regimen of vancomycin,
cefepime, and metronidazole. On day 2, the patient's WBC count increased
to 49,000/mL (4,500-11,000/mL) and his procalcitonin was elevated to
\textgreater{}100ng/mL (\textless{}0.25 ng/ml). Blood cultures
identified \emph{Clostridium sordellii} as the causative organism, and
vancomycin was switched for clindamycin while meropenem was continued.

Over the next week, subsequent blood cultures showed no growth and the
patient's clinical status stabilized. The antibiotic regimen was
switched from meropenem to ertapenem for two weeks upon discharge,
followed by oral clindamycin to continue for chronic suppression of the
infection until resection of renal mass. Due to his cancer and dementia
progression, his family chose to pursue hospice care soon after the
hospital discharge.

\emph{DISCUSSION}

This report describes a patient with back pain and uncontrollable
shaking, ultimately diagnosed with a \emph{C. sordelli} infection and
successfully treated with a course of antibiotics. The majority
of\emph{C. sordelli} cases reported infect patients during childbirth or
gynecologic procedures \textsuperscript{1}; however, the patient
described in this case presented in the setting of a hemorrhagic
necrotic renal mass and its fistulization with the adjacent splenic
flexure of the colon. It is suspected that the gastrointestinal tract
was the source of this patient's \emph{Clostridial} infection that
likely reached the bloodstream post colonic fistulization with the
necrotic, hemorrhagic renal mass.

The pathogenicity of~\emph{C. sordellii~} has been mainly attributed to
its hemorrhagic and lethal toxins that are known to cause local
necrosis~and edema \textsuperscript{1}. These toxins share immunological
cross reactivity with \emph{C. difficile} toxin A and B, being a part of
the large family of \emph{Clostridial} glucosylating toxins. These
toxins work at the cellular level using similar molecular mechanisms
involving glucosylation of Rho and/or Ras GTPAses. When infected,
patients may first notice nonspecific symptoms that quickly evolve into
massive tissue edema, effusions from the capillary leak, profound
leukocytosis, hemoconcentration, refractory hypotension, and
tachycardia. Typically, on initial presentation patients
infected\emph{with C. sordelli} are already experiencing symptoms of
toxic shock, as this patient did, due to its rapidly progressive
nature\textsuperscript{1,10}. A recent article reported that leukemoid
reactions, defined as a WBC count \textgreater{}50,000/ml, were highly
suggestive of fatality. This article described 45 cases, which had a
mortality rate of 69\%. Of these patients, 80\% had a leukemoid
reaction, and the majority died within 2-6 days of
infection\textsuperscript{1}.

As this patient's history does not follow the typical presentation, this
report emphasizes the importance of recognizing the signs and symptoms
of this infection and acting quickly due to its high mortality
rate.\emph{C. sordelli} must be considered in patients who present in
septic shock following a recent surgery or procedure, given the fact
that there is no rapid diagnostic test for this infection
\textsuperscript{1}. This creates a barrier to rapid diagnosis, which
can cause a delay in treatment. Upon suspicion of this diagnosis,
empiric antibiotic therapy should be started while awaiting blood
cultures. While little information exists to support a standard
treatment regimen, studies suggest \emph{C. sordelli} is susceptible to
beta-lactams, clindamycin, tetracycline, and chloramphenicol, and
resistant to aminoglycosides and sulfonamides \textsuperscript{9}.
Although further investigation is warranted, use of anti-clostridial
toxins as a form of treatment has been suggested \textsuperscript{1,3},
and may help guide treatment in such patients.

\emph{}

\emph{AUTHOR CONTRIBUTIONS}

Author 1: Wrote and prepared manuscript for submission, edited
manuscript.

Author 2: Helped prepare manuscript, edited manuscript.

Author 3: Edited manuscript, provided support to authors 1 and 2 as our
attending

\emph{ACKNOWLEDGEMENTS}

We have no acknowledgements to declare.

\emph{CONFLICTS OF INTEREST}

We have no conflicts of interest to declare.

\emph{REFERENCES}

1. Aldape MJ, Bryant AE, Stevens DL. Clostridium sordellii infection:
epidemiology, clinical findings, and current perspectives on diagnosis
and treatment. Clin Infect Dis. 2006 Dec 1;43(11):1436--46.

2. Smith LD, Holdeman LV. The pathogenic anaerobic bacteria. The
pathogenic anaerobic bacteria {[}Internet{]}. 1969 {[}cited 2021 Nov
17{]}; Available from:
https://www.cabdirect.org/cabdirect/abstract/19702201472

3. Sinave C, Le Templier G, Blouin D, L\selectlanguage{ngerman}éveillé F, Deland E. Toxic shock
syndrome due to Clostridium sordellii: a dramatic postpartum and
postabortion disease. Clin Infect Dis. 2002 Dec 1;35(11):1441--3.

4. Brett MM, Hood J, Brazier JS, Duerden BI, Hahné SJM. Soft tissue
infections caused by spore-forming bacteria in injecting drug users in
the United Kingdom. Epidemiol Infect. 2005 Aug;133(4):575--82.

5. Bangsberg DR, Rosen JI, Aragón T, Campbell A, Weir L,
Perdreau-Remington F. Clostridial myonecrosis cluster among injection
drug users: a molecular epidemiology investigation. Arch Intern Med.
2002 Mar 11;162(5):517--22.

6. Myers G, Ngoi SS, Cennerazzo W, Harris L, DeCosse JJ. Clostridial
septicemia in an urban hospital. Surg Gynecol Obstet. 1992
Apr;174(4):291--6.

7. Aldape MJ, Bryant AE, Ma Y, Stevens DL. The leukemoid reaction in
Clostridium sordellii infection: neuraminidase induction of
promyelocytic cell proliferation. J Infect Dis. 2007 Jun
15;195(12):1838--45.

8. Guzzetta M, Williamson A, Duong S. Clostridium Sordellii as an
Uncommon Cause of Fatal Toxic Shock Syndrome in a Postpartum 33-Year-Old
Asian Woman, and the Need for Antepartum Screening for This Clostridia
Species in the General Female Population. Lab Med. 2016
Aug;47(3):251--4.

9. Nakamura S, Yamakawa K, Nishida S. Antibacterial Susceptibility of
Clostridium sordellii Strains. Zentralblatt für Bakteriologie,
Mikrobiologie und Hygiene Series A: Medical Microbiology, Infectious
Diseases, Virology, Parasitology. 1986 May 1;261(3):345--9.

10. McGregor JA, Soper DE, Lovell G, Todd JK. Maternal deaths associated
with Clostridium sordellii infection. Am J Obstet Gynecol. 1989
Oct;161(4):987--95.

\emph{FIGURE LEGENDS}

Figure 1. Abdominal CT scan in a) coronal view and b) axial view. Arrows
point to the area of the necrotic renal mass invading the colon.\selectlanguage{english}
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